A Physiologically Based Approach To the Study of Bisphenol a and Other Estrogenic Chemicals On the Size of Reproductive Organs, Daily Sperm Production, and Behavior

Abstract

Two chemicals previously shown to have estrogenic activity, bisphenol A and octylphenol, were examined for their effects on accessory reproductive organs and daily sperm production in male offspring of mice fed these chemicals during pregnancy. These chemicals are used in the manufacture of plastics and other products, and have been detected in food and water consumed by animals and people. From gestation day 11-17 female mice were fed an average concentration (dissolved in oil) of bisphenol A or octylphenol of 2 ng/g body weight (2 ppb) and 20 ng/g (20 ppb). The 2 ppb dose of bisphenol A is lower than the amount reported to be swallowed during the first hour after application of a plastic dental sealant (up to 931 micrograms; 13.3 ppb in a 70 kg adult). We found that the 2 ng/g dose of bisphenol A permanently increased the size of the preputial glands, but reduced the size of the epididymides; these organs develop from different embryonic tissues. At 20 ng/g, bisphenol A significantly decreased efficiency of sperm production (daily sperm production per g testis) by 20% relative to control males. The only significant effect of octylphenol was a reduction in daily sperm production and efficiency of sperm production at the 2 ng/g dose. A new approach to studying physiologically relevant doses of environmental endocrine disruptors is discussed, particularly with regard to the development of the reproductive organs, the brain, and behavior.

Effects of perinatal exposure to bisphenol A on sociosexual behavior of female and male rats.

“…In males the slight changes observed point to an effect of prenatal BPA in inducing more defensive-type strategies during agonistic encounters and in slowing the copulatory sequence, but we also observed a reduction of sexual performance in postnatally treated animals. On the whole, in both sexes, sexual activity seems quite sensitive to perinatal exposure to BPA, in line with recent research showing significant effects on behavior and on reproductive indices after early BPA administration (9,10,18,19). The direction of the observed modifications in the two sexes in our experiment suggests that the effect of early BPA exposure on adult behavior may not be mediated by a classic organizational process activated by estrogenic action.…”

Lack of significant alteration in the prostate or testis of F344 rat offspring after transplacental and lactational exposure to bisphenol A.

“…Nagel et al (1997) have described exposure of pregnant CF 1 mice to BPA (2, 20 µg/kg/ day) during GD 11-17 to result in an increase in prostate weights of mature pups. vom Saal et al (1998) further reported reduced sperm efficiency in a subset of offspring exposed to BPA during pregnancy, for which enlarged prostates had been observed. However, Ashby and Tinwell (1998) argued that there were experimental deficiencies in their work.…”

Parent Bisphenol A Accumulation in the Human Maternal-Fetal-Placental Unit

“…Experiments demonstrating that minuscule amounts of parent BPA alter the reproductive organs of developing mice recently sparked the greatest alarm concerning this substance. Exposure of rodent fetuses to BPA at a very low dose (below the no-observed-adverse-effect level) typical of environmental exposure was found to produce postnatal estrogenic effects: reduced daily sperm production in males, increased prostate gland weight, alteration in the development and tissue organization of the mammary gland, disruption of sexual differentiation in the brain, long-term deleterious effects in the vagina, and accelerated growth and puberty in females (Howdeshell et al 1999;Kubo et al 2001;Markey et al 2001;Nagel et al 1997;Schonfelder et al 2002;Talsness et al 2000;vom Saal et al 1998;Welshons et al 1999). Some groups, however, were unable to reproduce the effects on the reproductive tract (Ashby et al 1999;Cagen et al 1999aCagen et al , 1999b, leading to a controversial discussion of their potentially harmful effects.…”